In Vitro and In Silico Evaluation of the Trypanocidal Activity of a Subfraction Isolated from Mutisia campanulata

TL;DR

A plant extract was tested for its ability to kill a parasite causing Chagas disease, with promising results from both lab and computer simulations.

Contribution

A subfraction from Mutisia campanulata was identified as a potential new treatment for Chagas disease through in vitro and in silico studies.

Findings

The subfraction showed strong trypanocidal activity with an IC50 of 5.88 ± 0.13 μg/mL against Trypanosoma cruzi.

Pseudotaraxasterol from the subfraction bound effectively to a T. cruzi enzyme with an energy of −10.2 kcal/mol.

Molecular dynamics simulations confirmed stable interactions between pseudotaraxasterol and the enzyme.

Abstract

In the present study, a subfraction rich in aliphatic
hydrocarbons
and pentacyclic triterpenes was isolated after chromatographic steps
from Mutisia campanulata Less and its trypanocidal
activity were evaluated using in vitro and in silico approaches. The chemical structures of the compounds
present in the subfraction were defined by GC–MS and 13C NMR data analysis. The trypanocidal activity in vitro of the subfraction indicated potency against epimastigote forms
of the Y strain from Trypanosoma cruzi (IC50 of 5.88 ± 0.13 μg/mL). Molecular docking studies were
conducted using four T. cruzi enzyme targets (1TC1, 1YHL, 2EF6 and 4C27) and six compounds,
including a control. The pseudotaraxasterol obtained better results
with an energy of −10.2 kcal/mol for the 4C27 enzyme. The RMSD
trajectory of the pseudotaraxasterol in protein–ligand complex
indicates stability during the 100 ns molecular dynamics simulation
and several weak van der Waals interactions predominate in protein–ligand
interactions. MMPBSA-per-residue decomposition analysis was used to
provide insight into the interactions between the binding site and
the pseudotaraxasterol. The findings revealed that the amino acid
residues MET-106, LEU-356, and TYR-103 play a critical role in effective
binding interactions. Therefore, pseudotaraxasterol holds potential
for the development of new prototypes for the treatment of Chagas
disease.

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